Objective. Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of primary hyperalphalipoproteinemia and represents a unique tool to evaluate how structural HDL alterations impact on HDL atheroprotective activity. Aim of the present study was to assess the vasculoprotective activity of HDL isolated from carriers of genetic CETP deficiency. Subjects and Methods. HDL and HDL subfractions were isolated from carriers of the R37X, Q165X and IVS7+1 CETP mutations. HDL and HDL subfractions from carriers were tested for their protein/lipid composition and for their anti-inflammatory and NO-promoting activity in endothelial cells. Results. HDL and HDL3 from carriers proved to be as effective as control HDL in down-regulating cytokine-induced VCAM-1 and in enhancing eNOS expression in endothelial cells. Carriers HDL2 were instead more effective than control HDL2 in inhibiting VCAM-1 and enhancing eNOS expression with a gene-dose dependent effect. These findings appear to be related to the peculiar lipid composition and the very high content in apoE of the HDL2 particles isolated from carriers of CETP deficiency. On the contrary, carrier HDL2 were less effective than control HDL2 in stimulating eNOS activation, likely because of a reduced S1P content. Conclusions. Large, apoE enriched HDL that accumulate in genetic CETP deficiency are very efficient in maintaining endothelial cell homeostasis, supporting the use of pharmacological CETP inhibition to increase HDL levels and enhance HDL-mediated atheroprotection.

Ossoli A, Pozzi S, Nilsson P, Jessup W, Kuivenhoven JA, Spina R, et al. (2011). VASCULOPROTECTIVE FUNCTION OF HDL FROM CETP-DEFICIENT SUBJECTS. In Giornale Italiano dell'Arteriosclerosi (pp.82-82). Pavia : EDIMES.

VASCULOPROTECTIVE FUNCTION OF HDL FROM CETP-DEFICIENT SUBJECTS

SPINA, Rossella;VALENTI, Vincenza;CEFALU', Angelo Baldassare;AVERNA, Maurizio;
2011-01-01

Abstract

Objective. Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of primary hyperalphalipoproteinemia and represents a unique tool to evaluate how structural HDL alterations impact on HDL atheroprotective activity. Aim of the present study was to assess the vasculoprotective activity of HDL isolated from carriers of genetic CETP deficiency. Subjects and Methods. HDL and HDL subfractions were isolated from carriers of the R37X, Q165X and IVS7+1 CETP mutations. HDL and HDL subfractions from carriers were tested for their protein/lipid composition and for their anti-inflammatory and NO-promoting activity in endothelial cells. Results. HDL and HDL3 from carriers proved to be as effective as control HDL in down-regulating cytokine-induced VCAM-1 and in enhancing eNOS expression in endothelial cells. Carriers HDL2 were instead more effective than control HDL2 in inhibiting VCAM-1 and enhancing eNOS expression with a gene-dose dependent effect. These findings appear to be related to the peculiar lipid composition and the very high content in apoE of the HDL2 particles isolated from carriers of CETP deficiency. On the contrary, carrier HDL2 were less effective than control HDL2 in stimulating eNOS activation, likely because of a reduced S1P content. Conclusions. Large, apoE enriched HDL that accumulate in genetic CETP deficiency are very efficient in maintaining endothelial cell homeostasis, supporting the use of pharmacological CETP inhibition to increase HDL levels and enhance HDL-mediated atheroprotection.
Settore MED/09 - Medicina Interna
2011
25° Congresso Nazionale SISA
Roma
30 Novembre- 3 dicembre 2011
2011
2011
1
Ossoli A, Pozzi S, Nilsson P, Jessup W, Kuivenhoven JA, Spina R, et al. (2011). VASCULOPROTECTIVE FUNCTION OF HDL FROM CETP-DEFICIENT SUBJECTS. In Giornale Italiano dell'Arteriosclerosi (pp.82-82). Pavia : EDIMES.
Proceedings (atti dei congressi)
Ossoli A; Pozzi S; Nilsson P; Jessup W; Kuivenhoven JA; Spina R; Valenti V; Cefalù AB; Averna M; Sirtori CR; Franceschini G; Calabresi L; Gomaraschi M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/104737
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